At present lung cancer is considered to be one of the most important causes of death, especially in adults at the ages from 50 to 69 years old. Long term exposure to smoking is the cause of lung cancer for 90% of the cases. Among male smokers, the lifetime risk of developing lung cancer is about 17%; among female smokers the risk is about 11%. For non-smokers, the risk of developing lung cancer is about 1%. The main causes for lung cancer in non-smokers are genetic factors, radon gas, asbestos, air pollution and passive smoking. There are two main types of lung cancer: non-small cell lung cancer (NSCLC) (in about 80% of the cases) and small cell lung cancer (in about 17% of the cases). NSCLC can further be classified according to the growth type and spread of the cancer cells. NSCLC can therefore be classified into squamous cell carcinoma, large cell carcinoma and adenocarcinoma. Adenocarcinoma is more frequent in women, Asians and non-smokers. Other less common types of NSCLC are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma.
It is generally known that most types of lung cancer have a poor prognosis. The 5 year survival for small cell lung cancer is less than 5%. Numbers are better for NSCLC. When the tumor is detected when it is still small and has not spread to the lymph nodes (Stage IA), the 5 year survival is 60%. This number drops rapidly with increasing size of the tumor and lymph node involvement. An early detection prior to the metastasis of the tumor is therefore very important, especially since at an early stage the tumor may be removed entirely by resection. Most non-small cell lung cancers, about 50%, however are only detected after metastasis. In these cases the 5-year survival of NSCLC is only 10 to 15%. However, even when NSCLC is detected at an early stage, the 5-year survival rate of the patients is low compared to other types of cancer. Even more, it is known that long-term (>5 years) NSCLC patients do not experience the same length of life and quality of life as their age-matched peers or other cancer survivors.
When NSCLC is detected at an early stage (IA to IIIA), the tumor is resected. The resection if followed by chemotherapy for larger tumors and in case the tumor has spread to the lymph nodes (stages II and IIIA). Patients in stage I receive no further treatment. Although these patients have a good prognosis based on tumor staging, a large percentage of patients develop metastases within several months or years. The consequence is a short survival time after resection. For this group of patients, follow up targeted pharmacotherapy treatment would be beneficial. Indeed, 30% to 40% of patients treated with first-line therapy will subsequently be candidates for second-line treatment. The United States Food and Drug Administration approved second-line treatments with docetaxel, pemetrexed, and an example of a targeted pharmacotherapy, erlotinib (an Epidermal Growth Factor Receptor (EGFR) inhibitor). Gefitinib, another targeted pharmacotherapy, an EGFR tyrosine kinase inhibitor, currently has only limited clinical use. The benefit in overall survival difference as shown in clinical trials was 7.5 months for docetaxal versus 4.6 months for control, 8.3 months for pemetrexed versus 7.9 months for control and 6.7 months for erlotinib versus 4.7 months for control.
Clinical trial studies have clearly shown individual patient benefiting from erlotinib (commercial name Tarceva) treatment if patients can be selected based on certain response prediction markers. The use of a erlotinib as a neoadjuvant therapy are being evaluated in clinical trials in stage I-III NSCLC patients prior to undergoing definitive treatment with surgery and/or radiation
At present there are however no clinical or analytical tools are available to make the distinction between responders and non-responders prior to deciding which treatment to administer. A few attempts of predictive biomarkers have been described in the literature such as EGFR expression, (assessed by immunohistochemistry, IHC) and c-K-ras gene mutations and EGFR mutations. These methods are however highly variable, not robust and show poor predictivity since these screenings are based on the detection of a limited number of proteins or genes. A small variation in the gene or protein expression will have profound effects on the screening method.
In view of the above, there remains a pressing need for methods that provide a fast and accurate prediction of the response of a patient diagnosed with NSCLC to neoadjuvant and adjuvant targeted pharmacotherapy. These methods would enable to provide information regarding the efficacy of the preoperative targeted pharmacotherapy treatment, and more specifically provide an early determination of the most suited treatment of the NSCLC patient.
The present invention aims at providing methods and devices for predicting the response of a patient diagnosed with NSCLC to induction targeted pharmacotherapy. The present invention also aims to provide methods and devices for predicting the response of patients diagnosed with NSCLC to specific medicaments. The method of the present invention therefore adds to the existing assays currently used to select therapies in NSCLC patients.